Within the context of clinical trials, the section evaluates methodological issues relevant to both research and treatment, such as monitoring drug use. In one study, we compared the efficacy of sweat versus urine for detecting illicit opiate use. Paired sweat patches that were applied and removed weekly (on Tuesdays) were compared to 3-5 consecutive urine specimens collected Mondays, Wednesdays, and Fridays in 44 patients in a methadone maintenance program. All patches were analyzed by ELISA immunoassay (cutoff concentration 10 ng/mL) and a subset were analyzed by GC/MS. Urine specimens were subjected to qualitative analysis by EMIT (cutoff 300 ng/mL). Opiates were detected in 38.5% of the sweat patches with the ELISA screen. GC-MS analysis confirmed 89.2% of the screen-positive sweat patches for heroin, 6-acetylmorphine, morphine and/or codeine (cutoff concentration 5 ng/mL) and 90.2% of the screen-negative patches. The overall efficiency of the sweat ELISA opiate immunoassay as compared to the sweat GC-MS analysis was 89.5%. Heroin and/or 6-acetylmorphine were detected in 78.1% of the GC/MS positive sweat patches. Median concentrations of heroin, 6-acetylmorphine, morphine and codeine in the positive sweat samples were 10.5, 13.6, 15.9 and 13.0 ng/mL, respectively. Agreement in duplicate sweat patch test results was 90.6% by ELISA analysis. The sensitivity, specificity and efficiency of sweat ELISA opiate results as compared to sweat GC-MS results were 96.7%, 72.2% and 89.5%. The sensitivity, specificity and efficiency between ELISA sweat patches and EMIT urine results were 68.6%, 86.1% and 78.6%. There were 13.5% false negative and 7.9% false positive sweat results as compared to urine tests. Analysis of sweat patches provides an alternate method for objectively monitoring drug use and provides an advantage over urine drug testing by monitoring an individual's drug use over an extended period of time, up to one week or longer, and by clearly documenting heroin use by confirming the presence of heroin and/or 6-acetylmorphine. However, the percentage of false negative results, at least in this treatment population, indicates that weekly sweat testing may be slightly less sensitive than thrice weekly urine testing in detecting opiate use. (Huestis MA, Cone EJ, Wong CJ, Umbricht A, Preston KL. J Analytical Toxicology, in press). In another study, we investigated the disposition and elimination patterns of cocaine and metabolites in the body fluids of chronic high-dose cocaine users during acute cessation of use. Plasma and saliva specimens were collected over a 12-h period during cessation and analyzed by gas chromatography-mass spectrometry. Pharmacokinetic parameters were derived by noncompartmental analysis of plasma and saliva data. Results indicated a cocaine terminal T1/2 of 3.8 hours in plasma and 7.9 hours in saliva. The terminal T1/2 of benzoylecgonine was 6.6 hours in plasma and 9.2 hours in saliva. Compared with prior studies of acute low-dose cocaine administration, these findings suggest that cocaine's half-life is longer in active street users than in occasional users though the half-life of its main metabolite benzoylecgonine remains similar (as do cocaine saliva-to-plasma ratios). Thus, regular use of cocaine appears to alter the disposition and elimination of cocaine when compared to single or occasional use. (Moolchan ET, Cone EJ, Wtsadik A, Huestis MA, Preston KL. J Analytical Toxicology, in press).